Abstract Background and Aims While the United States has been experiencing an opioid epidemic, 29 states and Washington DC have legalized cannabis for medical use. This study examined whether state-wide medical cannabis legalization was associated with reduction in opioids received by Medicaid enrollees. Design Secondary data analysis of state-level opioid prescription records from 1993–2014 Medicaid State Drug Utilization Data. Linear time–series regressions assessed the associations between medical cannabis legalization and opioid prescriptions, controlling for state-level time-varying policy covariates (such as prescription drug monitoring programs) and socio-economic covariates (such as income). Setting United States. Participants Drug prescription records for patients enrolled in fee-for-service Medicaid programs...